The proposed research is an extension of our previous studies which have defined the neuroanatomical and neurohistochemical features of the innervation of penile erectile tissue. Using histochemical, immunohistochemical, dye tracing methods and lesion paradigms a map of the autonomic innervation of the penis has been generated. Evidence points to a coexistence of acetylcholine and vasoactive intestinal polypeptide in vasodilator nerves to the penis. The vasodilator pathway is quite separate anatomically from the vasoconstrictor pathway, located in the sympathetic chain. The existence of an alternate nerve pathway to the penis, via the hypogastric nerve, has been documented. It is believed that this newly described pathway participates in penile erection and may substitute for the major vasodilator pathway in instances of injury to the terminal spinal cord. Since there is considerable disagreement on the exact substances released by penile vasodilator nerves, the present studies will focus on the ability of acetylcholine and vasoactive intestinal polypeptide to effect relaxation of penile smooth muscle. More specifically, both substances will be tested for their ability to relax contracted smooth muscle strips of cavernous tissue in in vitro preparations and to affect electrically stimulated relaxations of penile smooth muscle. The discovery of a suprasacral pathway which travels via the hypogastric nerve to pelvic penile neurons offers a unique opportunity to study possible plastic changes in visceral innervation following spinal cord injury. We will investigate whether there are compensatory changes in penile innervation following nerve injury. One hypothesis is that after interruption of the pelvic nerve, an injury which models trauma to the terminal spinal cord, the ancillary penile vasodilator pathway in the hypogastric nerve will compensate for the loss of the main vasodilator pathway. Therefore, our pharmacological studies will be useful in understanding how putative neurotransmitter substances interact with penile smooth muscle. Study of the dual vasodilator pathways to erectile tissue may help clarify and estimate the effect on reproductive potency of an injury to the sacral spinal cord.